Prospective Comparative Evaluation of Post-extraction Bleeding in Cardiovascular-Compromised Patients with and without Antiplatelet Medications

Abstract

Background and Objective

A considerable number of patients consulting a dental surgeon are on antiplatelet therapy, and an interruption of these agents for 3 to 7 days has been practised by majority of them prior to dental surgical intervention fearing excessive bleeding, risking the patient for the occurrence of adverse thrombotic events. The dental and medical literature shows a very low risk of excessive bleeding associated on the continuation of antiplatelet therapy. The objective of this study is to compare the bleeding following single-firm molar tooth extraction in patients who interrupt and those who continue antiplatelet therapy perioperatively.

Methodology

This is a prospective descriptive study on 170 patients on long-term low-dose antiplatelet therapy with 2 groups, each containing 85 patients—Group 1 with patients who interrupted antiplatelet therapy for 5 days before extraction and Group 2, patients who continued it perioperatively. A single molar tooth extraction was done under local anaesthesia with a vasoconstrictor. Gauze pressure pack was placed for 60 min. Socket was observed every 15 min for 1 h to look for excessive post-extraction bleeding.

Results

No statistically significant differences were found in post-extraction bleeding between the patients who stopped antiplatelet therapy and those who continued it.

Conclusion

The bleeding risk when continuing long-term low-dose antiplatelet therapy following a single molar tooth extraction is minimal. Bleeding, if excessive, can be easily controlled by gauze pressure pack or other local haemostatic agents. Thus, dental extractions can be performed on these patients without interrupting the antiplatelet drug pre-operatively provided a thorough medical history, physician’s consent and coagulation profile have been obtained prior to the procedure.

Introduction

Cardiovascular diseases are one of the primary causes of mortality and morbidity worldwide. Antiplatelet therapy is routinely used in these patients for primary and secondary prevention of adverse cardiovascular thromboembolic events like myocardial infarction, stroke and death [1]. Myocardial infarction is the most common perioperative complication in patients with coronary artery disease associated with a mortality rate of around 15 to 25% [2].

Aspirin, due to its ability to inhibit aggregation of platelets and prevent thrombosis, is by far the most extensively studied and widely used antiplatelet agent. It has been recommended that aspirin be used indefinitely in patients with pre-existing cardiovascular diseases for secondary prevention of thromboembolic complications [3]. Routinely used antiplatelet agents like aspirin and clopidogrel act by irreversibly inhibiting platelet aggregation lasting for the life span of platelets delaying the primary platelet plug formation and prolonging bleeding time [4]. But the sudden interruption of aspirin is found to cause rapid recovery of cyclooxygenase activity with the synthesis of thromboxane-A2 by newly formed platelets increasing the risk of developing thromboembolic events on their withdrawal [5]. Dental surgeons and physicians overestimate the risk of bleeding and underestimate the risk of thromboembolic complications, often preferring to interrupt antiplatelet medications before any surgical intervention [6].

During a tooth extraction, major blood vessels are unlikely to be encountered and bleeding usually ceases within minutes. If excessive bleeding is encountered, bleeding sites are easily accessible and local haemostatic agents can be employed to arrest bleeding. Although it takes a longer time for local haemostasis to occur when platelet functions are inhibited by antiplatelet agents, since the clotting factors are not impaired, the unaffected platelets and coagulation cascade are activated and bring about haemostasis by forming a more stable fibrin clot preventing further bleeding.

This study aimed to monitor and compare post-extraction bleeding following exodontia in patients on antiplatelet therapy who discontinued it 5 days before extraction and patients who continued it perioperatively.

Methodology

In total, 170 patients on long-term (last 10 or more years) low-dose antiplatelet medication (aspirin 75–150 mg/clopidogrel 75 mg) requiring single molar tooth extraction were included in the study. Patients were divided into 2 groups. Group 1 included patients who interrupted antiplatelet therapy 5 days before the procedure on advice of the physician/cardiologist, and Group 2 included patients who continued antiplatelet therapy perioperatively with physician/cardiologist consent.

The study excluded patients with liver diseases, alcoholism, any concurrent medication affecting haemostasis such as oral/parenteral anticoagulants, oral contraceptives, known cases of bleeding and clotting disorders, excessively apprehensive, exhibiting nervous anxiety and patients who were not willing to be a part of this study.

Informed consent, physician’s consent, medical fitness and coagulation profile were obtained before the procedure to rule out any pre-existing bleeding disorders or coagulopathies. The patient’s cardiologist/physician was sent a written explanation of the nature of the procedure and assurance of haemostasis being achieved in the chair. Those patients where written consent to carry out extraction without stopping antiplatelet therapy was provided by the physician/cardiologists were grouped under Group 2. Blood pressure, bleeding time, clotting time were evaluated on the day of the procedure, pre-operatively. Single maxillary or mandibular molar tooth (Fig. 1a) was extracted under 2% lignocaine hydrochloride with 1:200,000 adrenalin vasoconstrictor. Local haemostatic measures included patients biting on the gauze for 60 min after extraction. Patients’ tooth sockets were observed at the end of 15 min, 30 min (Fig. 1b) and 1 h (Fig. 1c) after extraction by a blinded observer to identify excessive immediate, post-operative bleeding.

Fig. 1.

a Mandibular right third molar with deep cervical caries indicated for extraction. b Post-extraction bleeding at the end of 30 min of gauze. c No post-extraction bleeding at the end of 1 hour

Socket with mild ooze, i.e. bleeding that soaked the gauze but did not fill the mouth with blood at the end of 15 min, was compressed with gauze pressure for further 30 min. Silk sutures were used only in case of excessive bleeding that filled the mouth (Fig. 2a) or mild ooze not controlled by the pressure pack for 30 min to stabilise the clot and hold it in place (Fig. 2b, c).

Fig. 2.

a Excessive post-extraction bleeding after 15 min of pressure pack. b Socket thoroughly irrigated; loose clot removed. c Suturing

Patients were discharged with usual post-extraction written instructions like biting down on the gauze for an hour; no mouth rinses for 24 h, soft, cold diet for first 24 h, etc. Patients were requested to call back or visit casualty in case post-operative bleeding was noted after discharge. Post-operative medications prescribed included those that do not have reported incidence of interaction with antiplatelet agents—amoxicillin 500 mg thrice daily and paracetamol 500 mg twice/thrice daily as required. The patients were reviewed after 24 h to check for any bleeding. The data collection form included: name; outpatient number; contact details, age; gender; medical condition for which antiplatelet therapy was prescribed; comorbidities, antiplatelet agent with dosage; whether or not patient interrupted the antiplatelet therapy before extraction, number of days of interruption, blood pressure, bleeding and clotting time, details of post-extraction socket monitoring at the end of 15 min, 30 min, 1 h and if any additional haemostatic methods/agents were used.

Results obtained were subjected to statistical analysis using the Chi-square test. Kendall Tau-B test was done for assessing the symmetric measures between the two groups. A statistical package SPSS version 17.0 was used. p value less than .05 was considered significant.

Result

In total, 170 patients on long-term low-dose antiplatelet therapy were studied. Mean age in Group 1 was 64.16 years and Group 2 was 63.30 years. In total, 84.7% of patients in Group 1 were on aspirin therapy, 15.3% on clopidogrel, and 85.3% of patients in Group 2 were on aspirin, 14.7% on clopidogrel. All the patients were known cases of coronary artery disease. In total, 83.5% of cases gave a history of stable angina, 10%, history of angioplasty, and 6.5% of patients underwent bypass surgery. The mean blood pressure was 134/84 mmHg. There was an insignificant difference in bleeding time between Groups 1 and 2, i.e. patients who continued antiplatelet therapy had a mean increase in bleeding time by 35 s compared to the patients who interrupted it for 5 days (Fig. 3).

Fig. 3.

Bleeding and clotting time

In total, 30 patients from Group 1 and 28 patients from Group 2 gave a history of hypertension and were on antihypertensive medications. Blood pressure was measured before the procedure, and stress reduction protocol of effective communication was used to calm and relax the patients.

Lignocaine with 1:200,000 adrenalin was used as it is not known to cause any significant haemodynamic changes. We also followed the protocol of maximum dosing of adrenalin for adults with questionable/uncontrolled hypertension and/or cardiovascular disease—.04 mg, totalling to around three 2.5-ml syringes.

In total, 38 patients in Group 1 and 44 patients in Group 2 had mild bleeding after 15 min following extraction where a pressure pack was placed for an additional 30 min. At the end of 30 min, 8% of the patients showed mild insignificant ooze from the socket. No patients had bleeding at the end of 60 min and 24-h follow up (Fig. 4).

Fig. 4.

Comparison of post-extraction bleeding—Group 1 and Group 2

The Kendall’s Tau-B test (Table 1) showed no significant difference in symmetric measures between the two groups concerning bleeding over 60 min measured every 15 min.

Table 1.

Kendall’s Tau-B—symmetric measures

Group	Value	Asymmetric SE	Approx. T	Approx. Sig.
Group 1 Kendall’s Tau-B	.428	.031	8.079	.000
Group 2 Kendall’s Tau-B	.467	.030	8.867	.000

There was no statistically significant difference in bleeding between the two groups at the end of 15 min, 30 min, 1 h and 24 h irrespective of the dosage i.e. aspirin—75 mg, aspirin—150 mg and clopidogrel—75 mg (Tables 2, 3). In total, 89.4% of the patients required only gauze pack over 1 h for efficiently controlling bleeding irrespective of the group they belonged to. Simple interrupted suturing was done only in 11% of the patients who had mild bleeding at the end of 30 min—8 patients in Group 1 and 10 patients in Group 2 (Figs. 4, 5).

Table 2.

Comparison of post-extraction bleeding between antiplatelet agents after 30 min

Group	Antiplatelet		Yes	No	Total
Group 1	Aspirin 75 mg	Count %	5 62.5%	50 64.9%	55 64.7%
	Aspirin 150 mg	Count %	2 25.0%	15 19.5%	17 20.0%
	Clopidogrel 75 mg	Count %	1 12.5%	12 15.6%	13 15.3%
	Total	Count %	8 100%	77 100%	85 100.0%
Group 2	Aspirin 75 mg	Count %	5 71.4%	53 67.9%	58 68.2%
	Aspirin 150 mg	Count %	1 14.3%	14 17.9%	15 17.6%
	Clopidogrel 75 mg	Count %	1 14.3%	11 14.1%	12 14.1%
	Total	Count %	7 100.0%	78 100%	85 100.0%

Table 3.

Chi-square test for comparison of bleeding between antiplatelet agents at 30 min

Group	Value	p
Group 1 Pearson’s Chi-square	.162	.922
Group 2 Pearson’s Chi-square	.060	.970

Fig. 5.

Haemostatic method used

In total, 12 patients on dual antiplatelet therapy (DAPT) with aspirin and clopidogrel required tooth extraction. We followed the current protocol where all patients continued the antiplatelet therapy perioperatively. Post-extraction bleeding was well controlled in all 12 patients with gauze pressure pack alone (Table 4).

Table 4.

Post-extraction bleeding in patients on dual antiplatelet therapy with aspirin and clopidogrel

Sl. no.	Bleeding time	Clotting time	Bleeding at the end of 15 min	Bleeding at the end of 30 min	Bleeding at the end of 60 min	Bleeding at 24 h
1	1 min 50 s	3 min 20 s	Yes	No	No	No
2	1 min 46 s	4 min	Yes	Yes	No	No
3	1 min 40 s	3 min 30 s	Yes	No	No	No
4	1 min 35 s	3 min 40 s	Yes	No	No	No
5	1 min 30 s	3 min 15 s	Yes	No	No	No
6	1 min 45 s	3 min 20 s	Yes	Yes	No	No
7	1 min 40 s	3 min 10 s	Yes	Yes	No	No
8	1 min 20 s	3 min 25 s	Yes	No	No	No
9	1 min 35 s	3 min 40 s	Yes	No	No	No
10	1 min 30 s	3 min 20 s	Yes	No	No	No
11	1 min 50 s	3 min 30 s	Yes	Yes	No	No
12	1 min 30 s	3 min 35 s	Yes	No	No	No

Since ours was a comparative study between patients who continued and those who discontinued long-term antiplatelet medication, we did not include them in the study statistics.

Discussion

Cardiovascular diseases have become the leading cause of mortality and morbidity in India with coronary artery disease and stroke being predominant causes of death accounting for more than 80% of death due to cardiovascular causes. The Global Burden of Disease study estimate of the age-standardised cardiovascular death rate of 272 per 100 000 population in India is higher than the global average of 235 per 100 000 population [7]. With advances in medical science and increased life expectancy, we see a significant number of medically compromised patients seeking dental treatment. We need to be aware of the current treatment protocols for their appropriate management.

The objective of this study was to evaluate whether continuing low-dose long-term antiplatelet therapy would increase the risk of post-extraction bleeding and if so, measures to control it, thereby stopping the interruption of antiplatelet therapy for minor dental surgical procedures, preventing the associated adverse cardiac effects.

For standardising the study group, only those patients with a history of coronary artery disease on long-term low-dose antiplatelet therapy (75–150 mg—Aspirin/75 mg—clopidogrel) were included. Only aspirin and clopidogrel were included as both inhibit platelet aggregation irreversibly even though their mechanism of action varies. Maxillary and mandibular molars without any significant periodontal compromise were included.

Role of Antiplatelet Therapy in CAD

Antiplatelet therapy inhibits platelet aggregation and prevents thrombosis, playing a critical role in secondary prevention of acute myocardial infarction and stroke in patients with coronary artery disease. According to guidelines from the American Heart Association, the American College of Cardiology and the American College of Chest Physicians, aspirin therapy should be started and continued indefinitely without interruption unless absolutely contraindicated in all patients with established coronary artery or other atherosclerotic diseases [8]. Coronary artery disease includes angina pectoris, myocardial infarction, sudden cardiac arrest and chronic coronary heart disease with atherosclerosis forming the dominant underlying cause [9]. The Antithrombotic Trialists’ Collaboration studied the long-term benefits of aspirin on preventing adverse cardiovascular thromboembolic events based on around 200 meta-analyses and demonstrated a 25% reduction in death from any vascular cause, myocardial infarction and stroke with antiplatelet therapy. They also concluded that a lower-dose range of 75–150 mg daily has an effective antiplatelet effect with lesser bleeding risk than higher doses [10].

Dual antiplatelet therapy is usually indicated for a short period for around 6 months to 1 year following the coronary intervention and slightly beyond 1 year in some selected cases with a high risk of stent thrombosis, if the patient does not have high bleeding risk and then shifted back to single long-term antiplatelet therapy. Also, elective dental procedures are contraindicated for up to 6 months after coronary intervention. The chances of stent thrombosis are extremely high during the first 6 to 12 months following coronary intervention, and the current protocol recommends continuation of the therapy during tooth extraction.

Risk of Thromboembolic Events

On withdrawal of antiplatelet therapy, the restoration of platelet function is variable depending on its dosage, duration of interruption and patient’s inherent enzymatic response to it. After a single dose of aspirin, new platelet production has been found to recover by around 10% per day and may take up to 10 days for full restoration of platelet number and function with normal cyclooxygenase activity [11]. Withdrawal of these medications has shown a significant platelet rebound phenomenon which is characterised by increased thromboxane production, decreased fibrinolysis and a resultant clinical prothrombotic state.

Any surgical intervention is associated with platelet activation due to release of tissue platelet-activating factors, blood stasis, perioperatively maintained hypothermia and sepsis. Also, sympathetic stimulation associated with surgery promotes hypercoagulability by upregulating platelet activity and coagulation cascade and downregulation of fibrinolysis. This along with the withdrawal of long-term antiplatelet therapy results in a prothrombotic state placing the patient at a very high risk of thromboembolic events [2].

Various retrospective studies and meta-analyses have upheld the risk of secondary cardiovascular adverse events like myocardial infarction and death on sudden withdrawal of antiplatelet agents [8, 10, 12–19].

Vaclavic et al. following a meta-analysis of 50,000 patients with coronary artery disease found that aspirin withdrawal was associated with a threefold increase in the risk of death and myocardial infarction in a non-surgical setting [20]. The risk may be much higher in a surgical or perioperative period due to the above-mentioned surgery-induced hypercoagulative state associated with a fivefold to tenfold increased cardiac death rate [2].

As the platelets form an integral part of haemostasis mechanism, the inhibitory effect of antiplatelet therapy on the aggregation of platelets has been a cause of fear due to an increased risk of bleeding among the practitioners. Hence the practice of advising interruption of antiplatelet therapy a couple of days before a planned surgical intervention, ignoring or unseeing the increased risk of fatal thromboembolic events reported following interruption of antithrombotic agents.

Practice of Interruption of Antiplatelet Therapy

It was reported that 86% of dental surgeons who asked their patients to withhold antiplatelet agents did so following recommendations from patient’s medical practitioner/cardiologist, whose decision is based on their experience in general medicine and not dental surgery [21]. There is also no consensus on number of days of interruption of antiplatelet therapy, with people recommending 7 to 10 days of interruption arguing that any withdrawal for less than a week does not significantly reduce the risk of bleeding as the irreversibly acting agents have their effects on platelets for their lifetime; thus, altered platelets are still present in the circulating pool, whereas those recommending 3 days argue that with 3 days of interruption more than 50% of platelets are newly formed without the effect of antiplatelet agents and suffice for bringing about the initiation of the haemostatic process [22].

Risk of Bleeding with Antiplatelet Therapy

In patients on antiplatelet therapy, platelet plug formation is delayed, and thus, there is an increase in bleeding time, but soon the unaffected platelets and coagulation cascade take over to plug the defect. Recent studies have repeatedly and consistently shown that even though there was an increase in bleeding duration, it was well controlled with local haemostatic aids alone. None required ligation or blood transfusion. Bleeding complications are rare in patients undergoing dental surgery and with the local measures available for haemostasis, bleeding if encountered can be efficiently controlled [23, 24].

Lockhart et al. in his article on acquired coagulopathies suggested that several hours of minor post-operative bleeding was of little concern following dental extractions and prolonged or clinically significant post-operative bleeding was defined by the following features [25]:

• Bleeding that continues beyond 12 h;

• Causes the patient to report to the dental surgeon or casualty;

• Results in a large haematoma or ecchymosis within the oral soft tissue mucosa;

• Bleeding that requires a blood transfusion.

None of the 170 patients in our study irrespective of the group they belonged to, showed bleeding beyond 60 min’ post-extraction, none called or returned to the department or casualty, indicating that continuing a low dosage of antiplatelet therapy does not pose a high risk of post-extraction bleeding. There was no statistical difference between the various dosages of antiplatelet agents—aspirin 75 mg, 150 mg and clopidogrel 75 mg. A thorough medical history and examination are of paramount importance to rule out medical conditions which may alter the coagulative status of the patient so that the operating surgeon may be well prepared in advance for the management of excessive bleeding if any.

The National Health Services of Bradford and Airedale have given their guidelines for the management of patients on antiplatelet therapy which has been summarised in the flow chart [5]:

There are various other guidelines. To summarise, all guidelines specifically mention minor dental surgical procedures to be of relatively low bleeding risk and recommend continuing the therapy perioperatively.

Our study also showed low bleeding risk on continuing antiplatelet therapy, thus supporting the current guidelines. We only used gauze pressure for a duration of 60 min and sutured only those cases which showed a significant bleeding at the end of 15 min in contrary to other studies, where various other haemostatic agents were used to control bleeding. An increased duration of gauze pack is sufficient to control post-extraction in most patients with no known history of medical conditions altering their coagulative profile.

Limitation/Future Scope of Study

In our study, we qualitatively measured post-extraction bleeding by observing the presence or absence of bleeding. The quantity of blood loss was not measured as various factors like blood pressure, blood viscosity, cardiac output play a role in quantifying the blood loss. Our study was restricted to only those patients who gave a history of coronary artery disease and were on single antiplatelet therapy. Only a single tooth was extracted. We did not include other indications of antiplatelet therapy nor patients on dual antiplatelet therapy.

Conclusion

Dental and medical literature shows only a minimal risk of bleeding complications in patients with continued use of antiplatelet medication. Bleeding, if encountered, can be effectively and efficiently controlled by various local measures. Moreover, bleeding complications, while inconvenient, do not carry the same risks as thromboembolic complications which have occurred on withdrawal of these medications [9, 11]. When balancing the benefits and risks of continuing versus discontinuing antiplatelet medications perioperatively, the existing data support the continuation of antiplatelet therapy throughout the routine and invasive dental procedures, thus preventing or reducing the increased risk of potentially life-threatening cardiovascular complications. Thus, in consensus with the current guidelines for perioperative management of patients on antiplatelet therapy, we do not warrant the practice of interrupting antiplatelet therapy before any minor dental surgical procedures.

Author Contribution

AS and AV helped in concepts and clinical studies; AS contributed to design, literature search, data acquisition, data analysis and manuscript preparation; AS and PP were guarantor, gave definition of intellectual content and edited the manuscript; and AS, PP and AL reviewed the manuscript.

Compliance with Ethical Standards

Conflict of interest

No potential conflict of interest relevant to this article was reported.